Use of Triacontanol in Preparation of Medicaments for Treatment of Cancers

ABSTRACT

Use of triacontanol in preparation of human medicaments for treatment of cancers, especially liver cancer, intestinal cancer, and lung cancer. Triacontanol can be formulated into many formulations, such as oral tablets, capsules, drop pills, sustained-released formulation, injectable solution, injectable powder, suspension, and emulsion.

FIELD OF THE INVENTION

The present invention relates to use of a known chemical substance in preparation of human medicaments.

BACKGROUND OF THE INVENTION

Triacontanol, with a molecular formula of C₃₀H₆₂O, a structural formula of CH₃-(CH₂)₂₈-CH₂-OH, has been reported a lot in the prior art. All the reports focus on usage of triacontanol as a growth regulator and a nutritional agent for vegetables, fruits, plants and grain crops, and some reports also refer it as a pesticide. No study about use of triacontanol in preparation of human medicaments has been reported.

SUMMARY OF THE INVENTION

The object of the present invention is to overcome the above-mentioned shortage in the prior art and provide a new use of triacontanol in preparation of human medicaments for treatment of cancers.

The present invention relates to a use of triacontanol in preparation of human medicaments for treatment of liver cancers.

The present invention relates to a use of triacontanol in preparation of human medicaments for treatment of intestinal cancers.

The present invention relates to a use of triacontanol in preparation of human medicaments for treatment of lung cancers.

In order to help well understanding the substance of the present invention, pharmacological tests of triacontanol and their results are provided to explain the new use of triacontanol in the pharmaceutical field.

In vivo antitumor test of triacontanol (No. 352B):

Antitumor curative effect tests against murine hepatoma H₂₂, intestinal cancer C₂₆ by a thixotropic oil suspension, an emulsion, and a finish oil of triacontanol, and antitumor curative effect test against Lewis lung cancer by an emulsion of triacontanol

Experiment method: Edema and pain inhibition effect of the tumor models of murine hepatoma H₂₂, intestinal cancer C₂₆ and Lewis lung cancer by hypodermic inoculating in the murine in vivo

A cancer cell suspension is prepared from the tumor source by homogenate technique, and then is inoculated subcutaneously under the armpit. After 24 hours, medication is administrated according to a predesigned scheme, and finally, an inhibition rate statistic against the tumor is obtained by comparing with a negative control group. The results are shown in Table 1.

TABLE 1 Curative effect test against murine hepatoma H₂₂ by gavaging a thixotropic oil suspension of triacontanol Amount of the Weight of the animal (unit) animal (g) at the at the Weight of the Dosage Administration beginning/at beginning/at tumor (g) Inhibition Sample Mg/kg/d scheme last last X ± SD rate % 352B 200 Igx6qd 10/10 20.9/27.3 1.45 ± 0.26** 55.67 thixotropic agent 352B 150 Igx6qd 10/10 21.0/27.8 1.61 ± 0.17** 46.33 thixotropic agent 352B 100 Igx6qd 10/10 20.7/27.6 1.75 ± 0.21** 41.67 thixotropic agent 352B 50 Igx6qd 10/10 21.0/28.0 2.14 ± 0.28  28.0 thixotropic agent DDP 7 igx2 10/10 21.4/25.4 1.269 ± 0.13**  91.0 Negative Blank igx6qd 24/20 20.7/28.6 3.00 ± 0.34  control group solvent **compared with the negative control group, p value <0.01.

TABLE 2 Curative effect test against murine Lewislung cancer (hypodermically inoculated) by intravenous administration of a triacontanol emulsion Amount of the Weight of the animal (unit) animal (g) at the at the Weight of the Dosage Administration beginning/at beginning/at tumor (g) Sample Mg/kg/d scheme last last X ± SD Inhibition rate % 352B 200 ivx10qd 10/10  1.2/23.2 1.27 ± 0.18** 54.15 emulsion 352B 150 ivx10qd 10/10 19.2/23.8 1.30 ± 0.15** 53.07 emulsion 352B 100 ivx10qd 10/10 19.3/24.2 1.71 ± 0.17** 38.27 emulsion 352B 50 ivx10qd 10/10 19.6/24.3 1.82 ± 0.15** 34.30 emulsion DDP 7 ipx2 10/10 19.2/20.9 0.278 ± 0.14**  89.00 Negative Blank ivx10qd 20/20 19.5/25.0 2.77 ± 0.18  control solvent group **compared with the negative control group, p value <0.01.

TABLE 3 Curative effect test against murine hepatoma H₂₂ (inoculated under the armpit) by gavaging a triacontanol oil agent Amount of the Weight (g) Weight of Inhibition Dosage animal before After the tumor rate Group (mg/kg) (unit) administration administration (g) (%) P value NS Equivalent 8 18.89 ± 1.31 23.94 ± 2.75 1.52 ± 0.64 — — volume DDP 0.001 8 19.16 ± 1.47 49.26 ± 3.39 0.31 ± 0.19 79.76 <0.01^(Δ) Menstruum Equivalent 8 19.09 ± 1.29 23.42 ± 2.10 1.38 ± 0.62 — volume 352-B 50 8 19.07 ± 1.14 23.51 ± 1.99 0.72 ± 0.38 48.13 <0.01* low dosage 352-B 100 8 19.36 ± 1.76 23.20 ± 2.86 0.57 ± 0.28 58.95 <0.01* middle dosage 352-B 150 8 19.25 ± 1.31 23.52 ± 2.36 0.49 ± 0.25 64.59 <0.01* high dosage Note: ^(Δ)compared with the NS control group; *compared with the menstruum control group.

TABLE 4 Effect to the thymus index and spleen index of murine by gavaging a triacontanol oil agent Thymus Weight of index (g/10 g Spleen index Dosage thymus body P Weight of (g/10 g body Group (mg/kg) (mg) weight) value spleen (mg) weight) P value NS Equivalent 104.23 ± 20.34  47.72 ± 9.49 188.04 ± 43.69 84.95 ± 12.94 volume DDP 0.001 59.61 ± 22.45 30.66 ± 8.06 <0.05^(Δ)  88.90 ± 27.79 46.05 ± 8.18  <0.01^(Δ) Menstruum Equivalent 95.86 ± 18.83 43.76 ± 9.18 148.21 ± 31.97 66.94 ± 12.04 volume 352-B 50 102.14 ± 15.90  44.96 ± 6.72 >0.05* 153.52 ± 35.62 67.11 ± 13.67 >0.05* low dosage 352-B middle 100 86.87 ± 16.44 38.71 ± 8.08 >0.05* 139.98 ± 41.62 62.12 ± 17.54 >0.05* dosage 352-B 150 86.86 ± 16.14 37.70 ± 6.73 >0.05* 151.26 ± 32.16 65.71 ± 12.34 >0.05* high dosage Note: ^(Δ)compared with the NS control group; *compared with the menstruum control group.

TABLE 5 Curative effect test against murine intestinal cancer C26 (hypodermically inoculated) by gavaging a 352B oil agent Amount of the animal Weight of the (unit) animal (g) at the at the Weight of Dosage Administration beginning/at beginning/at the tumor (g) Inhibition sample mg/kg/d scheme last last X ± SD rate % 352B oil 150 igx10qd 10/10 19.3/25.1 1.43 ± 0.17** 46.24 agent 352B oil 100 igx10qd 10/10 19.4/25.3 1.57 ± 0.18** 40.98 agent 352B oil 50 igx10qd 10/10 19.7/25.5 1.76 ± 0.17** 33.83 agent DDP 7 ipx2 10/10 19.1/24.1 0.346 ± 0.13**  86.99 Negative Blank igx10qd 20/20 19.5/25.7 2.66 ± 0.22  control solvent group Note: **compared with the negative control group, p value <0.01.

The above tests prove that the triacontanol has prominent antitumor effect and obvious dose-effect relationship, and hasn't obvious effect to the important immune organ (such as thymus and spleen) of the tumor-bearing mice.

The present invention has the following advantages:

1. The present invention digs a new medical usage of triacontanol which is a known compound and exploits a new application field.

2. The triacontanol according to the present invention is safe and nontoxic, and has strong pharmacological action and good medical application prospect.

3. The triacontanol according to present invention may be formulated into many different formulations, such as oral tablets, capsules, drop pills, sustained-released formulation, injectable solution, injectable powder, injectable suspension, and injectable emulsion. The dosage is Oral Administration: 200 mg-1000 mg/day-person; Injection: 100 mg-600 mg/day-person.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT Embodiment 1

Preparation of a capsule: 100 g triacontanol is dissolved into a proper amount of peanut oil, at the same time, starch and a spot of cyclodextrin for granulating is added. The mixture are launched into a mixer to mix uniformly and dried at 60° C., then sifted by an 80-mesh sieve. Granules made from the above-mentioned triacontanol and its auxiliary material is filled into a hollow capsule (Hard capsules of standard 2 or 3) by employing an automatic capsule filling machine. 

1. A use of triacontanol in preparation of human medicaments for treatment of cancers.
 2. The use of triacontanol according to claim 1 in preparation of human medicaments for treatment of liver cancers.
 3. The use of triacontanol according to claim 1 in preparation of human medicaments for treatment of intestinal cancers.
 4. The use of triacontanol according to claim 1 in preparation of human medicaments for treatment of lung cancers. 